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- Title
Impact of atorvastatin treatment on platelet-activating factor acetylhydrolase and 15-F<sub>2trans</sub>-isoprostane in hypercholesterolaemic patients.
- Authors
Kom, Ghainsom D.; Schwedhelm, Edzard; Maas, Renke; Schneider, Lydia; Benndorf, Ralf; Böger, Rainer H.
- Abstract
What is already known about this subject • Isoprostanes are the product of free radical oxidation of arachidonic acid bound to phospholipids. • Their hydrolysis from phospholipids is presumably catalysed by phospholipases A2. • Atorvastatin reduces protein concentrations of secretory PLA2s and concentrations of LDL, with which PAF-AH (group VII phospholipase) is associated. What this study adds • Atorvastatin affects PAF-AH activity and this effect is strongly associated with its lipid-lowering effect, but it has no effect on groups IIA and V PLA2s' activity. • Thus, PAF-AH is no independent risk factor of cardiovascular diseases. • Moreover, a role of PAF-AH in the liberation of 15-F2t-isoP from phospholipids is excluded. Aims Isoprostanes are the product of free radical oxidation of arachidonic acid, whose hydrolysis from phospholipids is presumably catalysed by phospholipases A2 (PLA2s) such as group IIA or V PLA2s, or group VII PLA2[platelet-activating factor acetylhydrolase (PAF-AH), lipoprotein-associated phospholipase]. Atorvastatin reduces concentrations of low-density lipoprotein (LDL), with which PAF-AH is associated, and PLA2s' protein concentrations. We investigated the effect of atorvastatin on PLA2s and PAF-AH activity and the urinary excretion of 15-F2trans-isoprostane (15-F2t-IsoP, 8-iso-PGF2α, iPF2α-III). Methods Twenty-four hypercholesterolaemic individuals naive to lipid-lowering therapy were randomized to atorvastatin 40 mg or placebo for 6 weeks. The 15-F2t-isoP urinary excretion (gas chromatography/mass spectrometry), PAF-AH and group IIA and V PLA2 activities (photometry) were assessed at baseline and end-point. Results At end-point, 15-F2t-isoP urinary excretion concentrations as well as PLA2s' activity were unchanged under atorvastatin (mean change 0.21 ± 1.79 ng h−1, 95% confidence interval −0.92, 1.35 and 0.33 ± 0.94 nmol min−1 ml−1, −0.27, 0.93) and under placebo (mean change 0.69 ± 1.69 ng h−1, −0.52, 1.90 and 1.29 ± 2.16 nmol min−1 ml−1, −0.25, 2.84). Atorvastatin treatment decreased total ( P < 0.001) and LDL-cholesterol ( P < 0.001) but had no effect on high-density lipoprotein. PAF-AH activity was lowered in the atorvastatin group (mean change − 5.27± 1.96 nmol min−1 ml−1, −6.51, −4.03, P < 0.001) but not in the placebo group (mean change 1.02 ± 1.64 nmol min−1 ml−1, 0.15, 2.20), and the change in PAF-AH activity was correlated with that in total ( P = 0.03) and LDL-cholesterol ( P = 0.03). Conclusion Our results show a lowering effect of atorvastatin on PAF-AH activity associated with its lipid-lowering effect and exclude a key role of PAF-AH in the liberation of 15-F2t-isoP from phospholipids.
- Subjects
ISOPROSTANES; EICOSANOIC acid derivatives; LIPOPROTEINS; PHOSPHOLIPASES; OXIDATIVE stress; OXIDATION-reduction reaction
- Publication
British Journal of Clinical Pharmacology, 2007, Vol 63, Issue 6, p672
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1111/j.1365-2125.2006.02832.x